Neutrophil-Lymphocyte Ratio and Absolute Lymphocyte Count as Prognostic Markers in Patients Treated with Curative-intent Radiotherapy for Non-small Cell Lung Cancer.

AIMS: The neutrophil-lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival. MATERIALS AND METHODS: A retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 2014 to 1 October 2016. A multivariate analysis was carried out to assess the ability of pre-treatment NLR/ALC, post-treatment NLR/ALC and change in NLR/ALC, adjusted for confounding factors using the Cox proportional hazards model, to predict disease recurrence and overall survival within 2 years of treatment. RESULTS: In total, 425 patients were identified with complete blood parameter values. None of the NLR/ALC parameters were independent predictors of disease recurrence. Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. Receiver operator curve analysis found a pre-NLR > 2.5 (odds ratio 1.71, 95% confidence interval 1.06-2.79, P < 0.05), a post-NLR > 5.5 (odds ratio 2.36, 95% confidence interval 1.49-3.76, P < 0.001), a change in NLR >3.6 (odds ratio 2.41, 95% confidence interval 1.5-3.91, P < 0.001) and a post-ALC < 0.8 (odds ratio 2.86, 95% confidence interval 1.76-4.69, P < 0.001) optimally predicted poor overall survival on both univariate and multivariate analysis when adjusted for confounding factors. Median overall survival for the high-versus low-risk groups were: pre-NLR 770 versus 1009 days (P = 0.34), post-NLR 596 versus 1287 days (P ≤ 0.001), change in NLR 553 versus 1214 days (P ≤ 0.001) and post-ALC 594 versus 1287 days (P ≤ 0.001). CONCLUSION: NLR and ALC, surrogate markers for systemic inflammation, have prognostic value in NSCLC patients treated with curative-intent radiotherapy. These simple and readily available parameters may have a future role in risk stratification post-treatment to inform the intensity of surveillance protocols.

New directions in the management of cleft lip.

Advances in cleft lip and palate have included improved understanding of its etiopathogenesis, genetics, and the surgical evolution of technical refinements in the correction of this deformity.

Clustered charge-to-alanine mutagenesis of the vaccinia virus A20 gene: temperature-sensitive mutants have a DNA-minus phenotype and are defective in the production of processive DNA polymerase activity.

Although the vaccinia virus DNA polymerase is inherently distributive, a highly processive form of the enzyme exists within the cytoplasm of infected cells (W. F. McDonald, N. Klemperer, and P. Traktman, Virology 234:168-175, 1997). In the accompanying report we outline the purification of the 49-kDa A20 protein as a stoichiometric component of the processive polymerase complex (N. Klemperer, W. McDonald, K. Boyle, B. Unger, and P. Traktman, J. Virol. 75:12298-12307, 2001). To complement this biochemical analysis, we undertook a genetic approach to the analysis of the structure and function of the A20 protein. Here we report the application of clustered charge-to-alanine mutagenesis of the A20 gene. Eight mutant viruses containing altered A20 alleles were isolated using this approach; two of these, tsA20-6 and tsA20-ER5, have tight temperature-sensitive phenotypes. At the nonpermissive temperature, neither virus forms macroscopic plaques and the yield of infectious virus is <1% of that obtained at the permissive temperature. Both viruses show a profound defect in the accumulation of viral DNA at the nonpermissive temperature, although both the A20 protein and DNA polymerase accumulate to wild-type levels. Cytoplasmic extracts prepared from cells infected with the tsA20 viruses show a defect in processive polymerase activity; they are unable to direct the formation of RFII product using a singly primed M13 template. In sum, these data indicate that the A20 protein plays an essential role in the viral life cycle and that viruses with A20 lesions exhibit a DNA(-) phenotype that is correlated with a loss in processive polymerase activity as assayed in vitro. The vaccinia virus A20 protein can, therefore, be considered a new member of the family of proteins (E9, B1, D4, and D5) with essential roles in vaccinia virus DNA replication.

The relationship between facial fractures and death from neurologic injury.

PURPOSE: The purpose of this study was to review patients who failed to survive blunt trauma and to determine whether there is a relationship between specific facial fracture patterns and death. PATIENTS AND METHODS: This was a retrospective record review of patients with facial fractures admitted to a level I trauma center between January 1, 1993 and December 31, 1996. Records were reviewed for gender, age, injury severity score (ISS), Glasgow Coma Scale (GCS), revised probability of survival (RPS), cause of death, and facial fracture pattern. Facial fracture patterns were grouped as lower face (mandible), midface (maxilla, zygoma, nose, and orbits), and upper face (frontal bone). Causes of death were grouped into neurologic, visceral, combined neurologic and visceral, and other. Surviving and nonsurviving groups were compared. Parametric data were analyzed with a pooled or separate variance t-test, nonparametric data with a Mann-Whitney U-test, and categorical variables with a chi-square test (P < or = .05). The odds ratio with corresponding 95% confidence intervals was used to show the association between facial fracture patterns and death. RESULTS: During the 4-year period, 6,117 patients were admitted with blunt trauma, 661 (11%) of whom had facial fractures. Those who died were more likely to be older than those who survived, with a lower GCS, lower RPS, and higher ISS. Although there was a male predominance in the patient population, there was no gender difference between those who died and those who survived. Surviving patients were more likely to have only isolated mandible injuries. Nonsurvivors were more likely to have isolated midface fractures or combinations of midface and other facial fractures. The odds ratio showed a 13 to 75 times greater risk of patients dying of neurologic injury with patterns other than isolated mandible injury than with any mid- or upper-facial fracture patterns. CONCLUSIONS: Compared with survivors, nonsurviving patients with facial fractures were older and had a lower GCS, higher ISS, and lower RPS. Nonsurviving patients had a dramatic predilection for mid- and upper-facial fracture patterns and death of neurologic injury.

Tyrosine phosphorylation of A17 during vaccinia virus infection: involvement of the H1 phosphatase and the F10 kinase.

Vaccinia virus encodes two protein kinases (B1 and F10) and a dual-specificity phosphatase (VH1), suggesting that phosphorylation and dephosphorylation of substrates on serine/threonine and tyrosine residues are important in regulating diverse aspects of the viral life cycle. Using a recombinant in which expression of the H1 phosphatase can be regulated experimentally (vindH1), we have previously demonstrated that repression of H1 leads to the maturation of noninfectious virions that contain several hyperphosphorylated substrates (K. Liu et al., J. Virol. 69:7823-7834). In this report, we demonstrate that among these is a 25-kDa protein that is phosphorylated on tyrosine residues in H1-deficient virions and can be dephosphorylated by recombinant H1. We demonstrate that the 25-kDa phosphoprotein represents the product of the A17 gene and that A17 is phosphorylated on serine, threonine, and tyrosine residues during infection. Detection of phosphotyrosine within A17 is abrogated when Tyr(203) (but not Tyr(3), Tyr(6), or Tyr(7)) is mutated to phenylalanine, suggesting strongly that this amino acid is the site of tyrosine phosphorylation. Phosphorylation of A17 fails to occur during nonpermissive infections performed with temperature-sensitive mutants defective in the F10 kinase. Our data suggest that this enzyme, which was initially characterized as a serine/threonine kinase, might in fact have dual specificity. This hypothesis is strengthened by the observation that Escherichia coli induced to express F10 contain multiple proteins which are recognized by antiphosphotyrosine antiserum. This study presents the first evidence for phosphotyrosine signaling during vaccinia virus infection and implicates the F10 kinase and the H1 phosphatase as the dual-specificity enzymes that direct this cycle of reversible phosphorylation.

An in vitro comparison of the effect of number and pattern of positional screws on load resistance.

OBJECTIVE: The purpose of this in vitro investigation was to determine whether the number or pattern of placement of positional screws affected their ability to resist vertical loads resembling mastication. MATERIALS AND METHODS: Standardized bone substitutes were secured with varying numbers of 17.0-mm-long, 2.0-mm outer diameter, self-tapping titanium screws (W. Lorenz Surgical, Jacksonville, FL) in various patterns using a positional screw technique. These patterns included one, two, three, four, and five screws in a linear pattern; two screws in a vertical pattern; three screws in an L-pattern, inverted-L pattern, backward-L pattern, inverted-backward-L pattern, and right and left diagonal pattern; four screws in a box pattern; and five screws in a domino pattern. Five models of each group were fabricated along with a control group. The models were secured in a jig and subjected to vertical loads by an Instron 8511.20 Mechanical Testing Unit (Canton, MA) until failure. Common engineering standards, including yield load, yield displacement, stiffness, maximum load, and displacement at maximum load, were measured, and means and standard deviations were derived and compared for statistical significance with an analysis of variance (ANOVA) and Scheffe multiple comparison test. RESULTS: Screw number and pattern of placement affected the mechanical characteristics in resistance to vertical load. Screw numbers less than three and all linear patterns were the least effective. The three-screw L patterns, as a category, provided greater resistance to vertical loads than either the three-screw linear or three-screw diagonal patterns. The addition of more than three screws in geometric patterns offered no greater benefit than the three-screw L patterns. CONCLUSIONS: In this in vitro study, the three-screw L patterns were the most effective and efficient when using the positional screw technique.

Warming intravenous fluids reduces perioperative hypothermia in women undergoing ambulatory gynecological surgery.

UNLABELLED: We evaluated whether warming i.v. fluids resulted in less hypothermia (core temperature < 35.5 degrees C) compared with room-temperature fluids. Thirty-eight adult outpatients undergoing elective gynecological surgery of > 30 min were randomized to two groups: fluid warming at 42 degrees C or control (room temperature fluids at approximately 21 degrees C). All patients received general anesthesia with isoflurane, tracheal intubation, standard operating room blankets and surgical drapes, and passive humidification of inspired gases. Tympanic membrane (core) temperatures were measured at baseline and at 15-min intervals after induction. The incidence of shivering and postoperative requirement for meperidine and/or radiant heat were evaluated. Core temperatures were lower in the control compared with the warm fluid group at the end of surgery (35.6 +/- 0.1 degrees C vs 36.2 +/- 0.1 degrees C; P < 0.05). More patients had final core temperature < 35.5 degrees C in the control compared with the warm fluid group (35% vs 0%; P < 0.05). There were no differences in time to discharge from the postanesthesia care unit or the incidence of shivering between the groups. We conclude that fluid warming, in conjunction with standard heat conservation measures, was effective in maintaining normothermia during outpatient gynecological surgery; however, there was no improvement in patient outcome. IMPLICATIONS: Women who received i.v. fluid at body temperature had significantly higher core temperatures during and after outpatient gynecological surgery compared with women who received i.v. fluids at the temperature of the operating room.

Diagnosis and management of blunt carotid artery injury in oral and maxillofacial surgery.

PURPOSE: Traumatic occlusion of the internal carotid artery (ICA) is a rare complication of maxillofacial trauma or surgery. This investigation evaluated patient demographics, diagnostic methods, and effective therapeutic modalities associated with blunt carotid injury (BCI). PATIENTS AND METHODS: This was a retrospective analysis of patient records with an ICD-9-CM diagnosis of carotid injury conducted at MetroHealth Medical Center during the 24-month period between August 1993 and July 1995. Carotid injuries attributable to penetrating trauma were excluded. Age, gender, cause of injury, Glasgow Coma Scale score, Injury Severity Score, type and location of injury, concomitant injury, diagnostic methods, treatment modalities, and outcome were identified, recorded, and analyzed. RESULTS: During the 24-month period, 12 patients (seven males and five females) suffered BCI. These patients were divided into two groups based on cause of the problem. In group I, there were 3,214 blunt trauma patients admitted during the 2-year study, of which 10 patients had BCI, representing 0.31% of blunt trauma patients, and 1.2% of patients with head injuries. Seven patients presented with hemiplegia, two with cranial nerve palsy, and one with perceptual neglect. Ninety percent of the patients had associated injuries. Two patients had surgical intervention, three received anticoagulation, and five had only supportive care. Four of the 10 patients died, four had moderate neurologic deficits, and two survived with only minor neurologic deficits. In group II, two patients developed BCI after surgery. A 52-year-old woman had a carotid injury after right total temporomandibular joint replacement, and a 48-year-old man who underwent surgical removal of a third molar became hemiplegic postoperatively. The first patient recovered after anticoagulation, whereas the second patient, who received only supportive care, has severe neurologic deficits. CONCLUSIONS: BCI is an uncommon entity. It is usually recognized when a patient develops an unexplained neurologic deficit, most often hemiplegia, subsequent to trauma or surgery of the head, face, or neck. In the early stages, the diagnosis can be missed by carotid ultrasound or computed tomography. The injury is unrelated to Glasgow Coma Scale score. Symptoms may not develop for days after injury in 50% of patients. Anticoagulation appears to be the most beneficial therapeutic modality.